The purpose of this study is to develop techniques for studying central nervous system monoamine metabolism in man, and to carry out pharmacokinetic studies of psychoactive drugs. The technique of giving probenecid intravenously to rapidly block transport of acid metabolites of dopamine and serotonin has been further explored this year in primates at doses ranging from 40-160 mg/Kg. Data derived from the lateral ventricle and lumbar space of the rhesus monkey suggest that quantitative data can be derived from lumbar CSF metabolite measurements in patients if CSF probenecid level is taken into account. Stable isotope techniques for studying brain amine metabolism have been further developed this year. Studies were concluded in rhesus monkeys on the feasibility of labelling CSF homovanillic acid (HVA) originating from brain dopamine metabolism with deuterated methionine. A quantitative estimate of HVA turnover in the lateral ventricle was calculated. The infusion of deuterium labelled HVA in patients was combined with an intravenous probenecid infusion to arrive at an estimate of central nervous system dopamine turnover in man. Diurnal studies of levels of catecholamine metabolites in the lateral ventricle of primates was completed. BIBLIOGRAPHIC REFERENCES: Perlow, M.J., Gordon, E.K., Ebert, M.E., Hoffman, H.J. and Chase, T.N.: The circadian variation in dopamine metabolism in the subhuman primate. J. Neurochem. 28: 1381-1383, 1977. Ziegler, M.G., Lake, C.R., Wood, J.H., Brooks, B.R. and Ebert, M.H.: Relationship between norepinephrine in blood and cerebrospinal fluid in the presence of a blood-cerebrospinal fluid barrier for norepinephrine. J. Neurochem. 28: 677-679, 1977.